AUTHOR=Wang Lin , Shen Weiyi , Zhang Rong , Cai Jiachang 

TITLE=Identification of a Novel Ceftazidime-Avibactam-Resistant KPC-2 Variant, KPC-123, in Citrobacter koseri Following Ceftazidime-Avibactam Treatment

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.930777

DOI=10.3389/fmicb.2022.930777

ISSN=1664-302X

ABSTRACT=<p>This study reported the identification of a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a <italic>Citrobacter koseri</italic> isolated from a patient in a Chinese hospital following ceftazidime-avibactam treatment of infection caused by OXA-232-producing <italic>Klebsiella pneumoniae</italic>. This novel KPC-123 consisting of 302 amino acids differs from KPC-2 by two insertions after positions 179 (ins179_TY) and 270 (ins270_DDKHSEA), respectively. Conjugation and cloning experiments confirmed that KPC-123 was able to confer high-level resistance to ceftazidime and ceftazidime/avibactam (MICs of 128 mg/L and 64/4 mg/L, respectively) and elevated MIC values of cefotaxime, cefepime, and aztreonam (4 mg/L, 2 mg/L, and 4 mg/L, respectively) but retained susceptibility to carbapenems. Whole-genome sequencing and genomic analysis revealed that <italic>bla</italic><sub>KPC−123</sub> within the “IS<italic>Kpn27</italic>-<italic>bla</italic><sub>KPC</sub>-IS<italic>Kpn6</italic>” structure was located on a 93,814-bp conjugative plasmid that was almost identical to a <italic>bla</italic><sub>KPC−2</sub>-carrying plasmid harbored in a <italic>K. pneumoniae</italic> isolate from the same sampling site of the patient, suggesting the transfer and <italic>in vivo</italic> evolution of this <italic>bla</italic><sub>KPC</sub>-carrying plasmid. Hence, active surveillance of ceftazidime/avibactam resistance and the underlying mechanisms, which may facilitate the prevention and control of the dissemination of resistance, is needed.</p>